1. Field of the Invention
The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases and disorders associated with kinase activity, particularly diseases associated with the activity of CDK1, CDK2, CDK4, CDK5, GSK3β, Bcr-abl, Flt-3, c-Kit, PDGFRβ, Mek1, CK1, c-Abl, KDR, IGF-1R, Flt-1, Tek, c-src, FGFR-1 and c-Met kinases.
2. Background
Kinases are involved in many aspects of cellular metabolism, proliferation, differentiation and development. A partial, non-limiting list of kinases include CDK1, CD 2, CDK4, CDK5, GSK3β, Bcr-abl, Flt-3, c-Kit, PDGFRβ, Mek1, CK1, c-Abl, KDR, IGF-1R, Flt-1, Tek, c-src, FGFR-1 and c-Met kinases. Many diseases are associated with abnormal cellular responses triggered by protein kinase-mediated events. Disease areas include autoimmune diseases, inflammatory diseases, neurological and neurodegenerative diseases, cancer, cardiovascular diseases, allergies and hormone-related diseases. In particular, kinases have been implicated in various diseases including: diabetes; Alzheimer's disease and mood disorders such as bipolar disorder; CNS disorders such as manic-depressive disorder and neurodegenerative diseases; cardiomyocyte hypertrophy; and development and regulation of sperm motility. Further, kinases been implicated in hair loss, schizophrenia and neurotrauma, for example, stroke, traumatic brain surgery and spinal cord trauma. These diseases may be caused by, or result in, the abnormal operation of certain cell signaling pathways, for example, those signaling pathways in which CDK1, CDK2, CDK4, CDK5, GSK3β, Bcr-abl, Flt-3, c-Kit, PDGFRβ, Mek1, CK1, c-Abl, KDR, IGF-1R, Flt-1, Tek, c-src, FGFR-1 and c-Met kinases play a role. Accordingly, molecules that modulate the activity of kinase-mediated signaling are useful as therapeutic agents in the treatment of such diseases.